Recent progress in the treatment of AIDS has resulted in prolonged survival and a more protracted course with multiple new clinical manifestations, including an increasing incidence of cardiac dysfunction. In the United States alone, it is estimated that 10-18% of HIV seropositive individuals will manifest evidence of left ventricular (LV) dysfunction, giving rise to 21,000-40,000 new cases of symptomatic heart failure each year by the year 2000 (25,38). Despite clinical recognition, the pathogenesis of HIV cardiomyopathy is unclear, limiting the application of both specific treatments and preventive strategies. Simian immunodeficiency virus (SIV) causes an AIDS-like illness in macaques generally characterized by a prolonged clinical latency, a weak neutralizing antibody response, persistent viremia, and tropism for bone marrow-derived cells. The applicants have observed physiological evidence of left ventricular dilatation and contractile dysfunction, as well as associated myocardial and vascular pathology in SIV-infected rhesus monkeys which is not seen in uninfected animals. This initial characterization of SIV cardiomyopathy constitutes the first description of an experimental model of cardiac dysfunction in AIDS and affords a unique opportunity to investigate its pathogenesis. Therefore, using the SIV-infected macaque model of AIDS, they propose to examine the physiological and cellular basis of AIDS-associated cardiomyopathy. They hypothesize that cardiac dysfunction following SIV infection is a consequence of chronic infection. This may occur by direct infection of myocytes by SIV; or more likely, indirectly through inflammatory mediators induced by SIV, and/or opportunistic infections arising as a consequence of progressive immunosuppression. To test their hypothesis they plan to: 1) Determine the temporal relationship between the development of LV contractile dysfunction and cardiac histopathology through a longitudinal study in rhesus monkeys infected with SIV; 2) Correlate the development of LV contractile dysfunction with changes in both circulating and transmyocardial cytokines and nitrogen oxides; 3) Examine the role of opportunistic infections (e.g. cytomegalovirus) on the development of cardiac dysfunction and; 4) Characterize the inflammatory cells associated with myocarditis and arteripathy observed in chronically SIV-infected rhesus monkeys. (End of Abstract)